Lopinavir/ritonavir pharmacokinetics in HIV and hepatitis C virus co-infected patients without liver function impairment: Influence of liver fibrosis

José Moltó, Marta Valle, Asunción Blanco, Eugenia Negredo, Meritxell DelaVarga, Cristina Miranda, José Miranda, Pere Domingo, Josep Vilaró, Cristina Tural, Joan Costa, Manuel José Barbanoj, Bonaventura Clotet

Research output: Contribution to journalArticleResearchpeer-review

22 Citations (Scopus)

Abstract

Background and objective: To assess the influence of hepatitis C virus (HCV) co-infection and the extent of liver fibrosis on lopinavir/ritonavir pharmacokinetics in HIV-infected patients without liver function impairment. Methods: Cross-sectional, comparative study enrolling HIV-infected adults receiving lopinavir/ritonavir (400mg/100mg twice daily). HIV/HCV co-infected patients were grouped as having advanced fibrosis (HCV+/FIB+, n = 7) or not (HCV+/FIB-, n = 8) based on the FIB-4 index. A full concentration-time profile was obtained for each patient, and blood samples were collected before (0), and 1, 2, 4, 6, 8, 10 and 12 hours after a lopinavir/ritonavir dose. Lopinavir and ritonavir concentrations in plasma were determined by high-performance liquid chromatography. Maximum and minimum plasma concentrations (Cmax and Cmin), area under the plasma concentration-time curve from 0 to 12 hours (AUC12), apparent oral clearance at steady state (CLss/F), and apparent volume of distribution after oral administration (Vd/F) were calculated for each individual using a non-compartmental approach. Results: Twenty-six HCV- and 22 HCV+ patients were enrolled. Lopinavir and ritonavir pharmacokinetics were comparable between HCV- and HCV+ patients. However, the Vd/F of lopinavir was 125% higher in HCV+/FIB+ patients than in HCV- patients (p = 0.015) and 107% higher than in HCV+/FIB- (p = 0.040) patients. The CLss/F of ritonavir was 40% lower in HCV+/FIB+ patients than in HCV- patients (p = 0.005) and 44% lower than in HCV+/FIB- patients (p = 0.040). Thus, for ritonavir AUC12, Cmax and Cmin in HCV+/FIB+ patients were 63%, 86% and 100% higher, respectively, when compared with those parameters in HCV- patients (p = 0.005, p = 0.012 and p = 0.015, respectively), and 80%, 86% and 100% higher, respectively, when compared with levels in HCV+/FIB-patients (p = 0.040, p = 0.040 and p = 0.029, respectively). Conclusion: Lopinavir exposure is similar in HIV-infected patients with or without HCV co-infection and without liver function impairment. However, ritonavir exposure may be higher in this setting, particularly in individuals with advanced liver fibrosis. © 2007 Adis Data Information BV. All rights reserved.
Original languageEnglish
Pages (from-to)85-92
JournalClinical Pharmacokinetics
Volume46
Issue number1
DOIs
Publication statusPublished - 18 Jan 2007

Fingerprint Dive into the research topics of 'Lopinavir/ritonavir pharmacokinetics in HIV and hepatitis C virus co-infected patients without liver function impairment: Influence of liver fibrosis'. Together they form a unique fingerprint.

Cite this